For years, infertility specialists have insisted in scientific and
public arenas that a key IVF procedure known as ovarian
stimulation—chemically goosing women’s ovaries to ripen multiple eggs in
a single menstrual cycle—poses little or no long-term cancer risk for
those undergoing it.

Like so many other safety claims advanced by
researchers and clinicians since the early days of reproductive
medicine, this assertion has been made on the basis of virtually no
solid evidence, and those who have accepted it can only have done so on
the basis of faith: Over the last two decades, the two dozen or so
scientific follow-up studies of women who have undergone ovarian
stimulation have yielded conflicting results and have been largely
unconvincing because they have looked at relatively small numbers of
women, have collected a limited range of medical information, and have
not tracked their subjects over a long period of time.

That
said, a dozen or so previous studies pointed to an increased risk for
both ovarian cancer and borderline ovarian tumors, malignancies that are
usually self-contained and operable and have higher survival rates than
full-blown ovarian cancers.

Now an impressively large and
comprehensive study out of the Netherlands has confirmed the disquieting
findings of those studies while affording a much sharper picture of the
risks posed by exposure to fertility drugs like clomiphene citrate,
synthetic gonadotropin releasing hormone analogs, and other stand-ins
for the naturally circulating hormones that, in fertile women, cause
eggs to ripen and be released. The article, published in the online version of Human Reproduction
on October 26, concludes that among the population of women in the
study, exposure to fertility drugs significantly heightened the chances
of borderline and invasive ovarian malignancies.

The 18-member team, led by epidemiologist F. E. van Leeuwen
of the Netherlands Cancer Institute in Amsterdam, went to exhaustive
lengths to assemble a longitudinal study that would have a high degree
of statistical power. Aided by extremely detailed records from Dutch
IVF clinics, the team identified an initial cohort of 19,861 women who
had been treated at least once with fertility drugs between 1983 and
1995, as well as a comparison group of 6604 other women who were
diagnosed as being subfertile during that same period but had not
received such treatment.

Ultimately, a total of 25,152 women
were represented in the final study, 19,146 in the IVF cohort and 6006
in the control group, and their medical histories from 1 January 1989 to
June 2007 examined. The researchers corrected for failings of earlier
studies by gathering information from both clinics and participants
about whether they had children or had experienced difficulty
conceiving, because both the lack of children and subfertility itself
have been posited as risk factors for ovarian cancer. They drew in data
on the women’s family histories and lifestyle factors and, for the
women who had undergone IVF or artificial insemination, obtained details
on the date, dosage, and type of fertility drugs received. Then, the
team linked these women to a national registry with computerized records
from all pathology labs in the country, which gave them great certainty
concerning ovarian cancer diagnoses and deaths. They made multiple
other adjustments to ensure the validity of their findings.

They
found that “women treated for ovarian stimulation for IVF have a 2-fold
increased risk of ovarian malignancies compared with subfertile women
not treated with IVF.” In addition, the type of tumor that appeared
most frequently—known as serous—is thought to originate specifically
from the layer of cells covering the ovaries and occurs less frequently
in general than the other type, called mucinous.

With treatment
for IVF on the rise globally, and births via egg donation also on the
rise, it would seem imperative that the industry amend its safety claims
regarding exposure to fertility drugs. Most of the young women who
took my “Women’s and Gender Studies” course this semester were quite
familiar with the advertisements run in the student newspaper and
elsewhere for egg donation, and knew about the bank account benefits of
the procedure. None had heard, coming into the course, about any
possible down side.

Certainly, the American Society for
Reproductive Medicine (ASRM) should consider doing more than it has done
to date to advertise the risks. If one goes to the ASRM website page
on “The Risks and Benefits of Donating Your Eggs,” which claims to have
been updated December 16, 2011, one is sent to an article on the
website i09, “a
daily publication that covers science, science fiction, and the future,”
albeit with the disclaimer: WARNING! THE ASRM HAS NOT REVIEWED THE
CONTENTS OF THE EXTERNAL WEB SITES LISTED ON THIS PAGE, NOR CAN WE
ENDORSE THEM OR THE VIEWS EXPRESSED WITHIN.

Why an organization whose mission statement
asserts that it “is committed to facilitating and sponsoring
educational activities for the lay public” would link to information
that it has not bothered to review is a matter for another blog, but,
for the record, the i09 article is happy to explain that:

Accelerated cancer proliferation is suggested in rare
cases due to the increase in hormone levels, but this is far from an
established correlation. Premature menopause and infertility are often
linked to egg donors, but we will not know if a correlation is present
until decades pass and more data is collected. The only confirmed
positive or negative effects of egg donation are psychological ones,
with most women benefiting from the joy of helping a couple in need.

Gina Maranto is Co-Director of Ecosystem Science and Policy and
coordinator of the Environmental Science and Policy program at the
University of Miami's Leonard and Jayne Abess Center. She is the author
of Quest for Perfection: The Drive to Breed Better Human Beings (1996).